Ocular Administration of Palonosetron in the Prevention of Cisplatin-Induced Nausea and Vomiting.

Cancer treatments are frequently associated with nausea and vomiting despite greatly improved preventive medication. Administration of antinausea agents as eye drops might provide easy and rapid access to the systemic circulation for prevention of nausea and vomiting and for the treatment of breakthrough nausea, but the ocular administration route has rarely been evaluated. Palonosetron is a second-generation 5-hydroxytryptamine 3 receptor antagonist approved for prevention and treatment of chemotherapy-induced nausea and vomiting. We compared ocular administration of palonosetron to non-active vehicle eye drops and to intravenous palonosetron in the prevention of cisplatin-induced nausea and vomiting in beagle dogs. Palonosetron ocular drops at the dose of 30 µg/kg reduced cumulative nausea over time as measured with the area under the visual analog scale curve by 98% compared with the vehicle and reduced nausea-associated dog behavior by 95%. Vomiting was completely prevented with repeated palonosetron ocular dosing. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) palonosetron formulation was well tolerated locally at the palonosetron concentration of 3 mg/ml. Absorption of palonosetron from eye drops was fast. Ten minutes after ocular administration, palonosetron plasma concentrations were similar compared with intravenous administration, and remained similar for six hours. We conclude that palonosetron is rapidly absorbed into the systemic circulation from eye drops. Ocularly administered palonosetron was well tolerated in the HP-ß-CD formulation and was highly effective in the prevention of cisplatin-induced nausea and vomiting. Evaluation of the safety and efficacy of ocular administration of palonosetron is warranted in the prevention and treatment of chemotherapy-induced nausea and vomiting in clinical trials. SIGNIFICANCE STATEMENT: Palonosetron, an effective and well-tolerated antiemetic drug was rapidly absorbed into the systemic blood circulation when administered as eye drops. The achieved palonosetron blood concentrations prevented cisplatin-induced nausea and vomiting in beagle dogs. Palonosetron eye drops might provide an easy and quick method for administering palonosetron when parenteral administration is desired and intravenous administration is not feasible.

Preoperative Predictors of Better Long-term Functional Ability and Decreased Pain Following LSS Surgery: A Prospective Observational Study with a 10-year Follow-up Period.

STUDY DESIGN: A prospective observational 10-year follow-up study. OBJECTIVE: This study aimed to examine preoperative predictors for better surgical outcomes in patients with lumbar spinal stenosis (LSS) 10 years after surgery. SUMMARY OF BACKGROUND DATA: LSS is a leading cause of low back surgery in patients older than 65 years. Limited data are available for predictors of long-term surgical outcomes in patients with LSS. METHODS: At the baseline, 102 patients with LSS underwent decompressive surgery, and 72 of the original study sample participated in a 10-year follow-up study. Study patients filled out a questionnaire preoperatively, and follow-up data were collected at 3 months, 6 months, 1 year, 2 years, 5 years, and 10 years postoperatively. Surgical outcomes were evaluated in terms of disability with the Oswestry Disability Index (ODI) and pain with the visual analog scale (VAS). Predictors in the models were nonsmoking status, absence of previous lumbar surgery, self-rated health, regular use of painkillers for symptom alleviation, and BMI. Statistical analyses included longitudinal associations, subgroup analyses, and cross-sectional analyses. RESULTS: Using multivariate analysis, statistically significant predictors for lower ODI and VAS scores at 10 years were nonsmoking status, absence of previous lumbar surgery, better self-rated health, and regular use of painkillers for <12 months. Patients who smoked preoperatively or had previous lumbar surgery experienced more pain and disability at the 10-year follow-up. CONCLUSION: These study results can enhance informed decision-making processes for patients considering surgical treatment for LSS by showing preoperative predictors for surgical outcomes up to 10 years after surgery. Smokers and patients with previous lumbar surgery showed a decline in surgical benefits after 5 years. LEVEL OF EVIDENCE: 3.

High Level of Childhood Trauma Predicts a Poor Response to Spinal Cord Stimulation in Chronic Neuropathic Pain.

BACKGROUND: Spinal cord stimulation (SCS) relieves pain by delivering doses of electric current to the dorsal column of the spinal cord and has been found to be most effective in the treatment of neuropathic pain. Psychological distress is a significant risk factor for the development of chronic pain and has been found to affect the outcome of SCS. Childhood trauma is a risk factor for chronic pain, but has not previously been studied in SCS patients. OBJECTIVES: The objective of this prospective registry-based study was to investigate the prevalence of 5 domains of childhood trauma (emotional neglect, emotional abuse, physical neglect, physical abuse, and sexual abuse) and their relationship with the outcome of spinal cord stimulation on patients suffering from treatment-resistant chronic pain. METHODS: SCS patients treated at Kuopio University Hospital between 1/1/2015 and 12/31/2016 were sent a survey in the mail, the Trauma and Distress Scale, assessing childhood trauma (n = 43). Neuropathic pain, disability, anxiety, and depression were measured in the patients pre-surgery and at 6 and 12 months post-surgery. The patients who provided their name on the questionnaire (n = 22) and had suffered from 3 or more domains of trauma were grouped as the high-trauma group (n = 13) and the rest as the low-trauma group (n = 9). RESULTS: The questionnaire was completed by 40 patients (93%). At least 1 domain of trauma was experienced by 35 (88%) patients, and at least 2 by 24 (60%). The low-trauma group displayed a statistically significant decrease in the mean PainDETECT score from 21.5 before SCS to 16.5 at 12 months post-surgery (Wilk's lambda = 0.297, F(2,9) = 10.6, P = 0.004), contrary to the high- trauma group (Wilk's lambda = 0.904, F(2,6) = 0.3, P = 0.739). LIMITATIONS: Only 22 of the 40 patients provided their name on the questionnaire, which decreased the sample size on follow-up. CONCLUSION: This was the first study to investigate childhood trauma in SCS patients. Patients who had experienced high amounts of childhood trauma did not experience any relief from neuropathic pain 12 months' post-SCS, contrary to the low-trauma group. Childhood trauma might be a factor worth screening in the preoperative evaluation and aftercare of SCS candidates. KEY WORDS: Spinal cord stimulation, the Trauma and Distress Scale, chronic pain, childhood trauma, childhood abuse, childhood neglect, chronic back pain, back pain, psychological distress, neuropathic pain.

Preoperative sense of coherence associated with the 10-year outcomes of lumbar spinal stenosis surgery.

A prospective 10-year follow-up study was conducted to determine the significance of the preoperative sense of coherence, with respect to the preoperative and 10-year clinical characteristics, among lumbar spinal stenosis patients ( N = 99). In addition, the predictive value of the preoperative sense of coherence regarding the 10-year surgery outcome was also evaluated. In a logistic regression analysis, a weak preoperative sense of coherence and low functional ability predicted the patients' functional ability 10 years after the surgery. Moreover, those patients with weak sense of coherence before surgery showed poorer functional ability 10 years after the surgery, but not preoperatively. A weak preoperative sense of coherence seems to associate with poorer long-term outcome after surgery; therefore, various rehabilitation strategies are discussed.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Depression is associated with the long-term outcome of lumbar spinal stenosis surgery: a 10-year follow-up study.

BACKGROUND CONTEXT: Depression is associated with greater postoperative disability in patients with lumbar spinal stenosis (LSS). No previous studies have reported the association in a 10-year follow-up. PURPOSE: To evaluate the association between preoperative and postoperative depressive symptoms and the surgical outcome among patients with LSS in a 10-year follow-up. In addition, we examined the effects of the depressive burden on the surgical outcome. DESIGN: A prospective observational follow-up study. PATIENT SAMPLE: A total of 102 patients with LSS underwent decompressive surgery, and 72 of the original sample participated in the 10-year follow-up study. OUTCOME MEASURES: Self-report measures: the Oswestry Disability Index (ODI) and visual analog scale (VAS). METHODS: Data were collected using a questionnaire that was administered seven times during the study period. Depressive symptoms were measured with the Beck Depressive Inventory (BDI). The depressive burden was calculated by summing the preoperative and all follow-up BDI scores. Statistical analysis included cross-sectional group comparisons and linear mixed models. The authors report no conflicts of interest related to this work. RESULTS: The high depressive burden group had a poorer outcome for pain, disability, and the walking distance at the 10-year follow-up. In linear mixed models, a higher preoperative BDI score associated with higher disability. Furthermore, higher postoperative BDI scores and the depressive burden were associated with higher disability and pain in the 10-year follow-up. CONCLUSIONS: Patients with LSS with even slightly elevated depressive symptoms have an increased risk of postoperative pain and disability in a 10-year follow-up. To improve the surgical outcome among these patients, screening for depression both preoperatively and during the rehabilitation following surgery is important.

Low sense of coherence during postoperative recovery is associated with a poorer lumbar spinal stenosis - surgical outcome: A 5-year follow-up study.

This study investigated the association between the 3-month postoperative sense of coherence and the 5-year postoperative outcome of decompressive surgery for lumbar spinal stenosis. The participants with a lower sense of coherence at the 3-month follow-up had a poorer functional ability and lower satisfaction with surgery, higher pain ratings, lower life satisfaction and more depressive symptoms 5 years postoperatively. A low 3-month sense of coherence associated with greater pain and a poorer functional ability 5 years postoperatively. Evaluating sense of coherence and depressive symptoms in patients who have had lumbar spinal stenosis surgery may help in identifying those in need of enhanced support for postoperative recovery.

Life dissatisfaction is associated with depression and poorer surgical outcomes among lumbar spinal stenosis patients: a 10-year follow-up study.

Life satisfaction is associated with overall somatic health and the short-term surgical outcome in lumbar spinal stenosis (LSS) patients. In this study, the long-term relationship between life satisfaction and the surgical outcome in LSS patients was investigated in a 10-year follow-up. This prospective clinical study included 102 LSS patients who underwent decompressive surgery. They completed a set of questionnaires first preoperatively and then 6 times postoperatively (at 3 and 6 months, and at 1, 2, 5 and 10 years). The final study population at the 10-year follow-up comprised 72 patients. A four-item life satisfaction scale was used to measure global life satisfaction. The sum of all seven life satisfaction scores provided a measure of the life dissatisfaction burden over the entire 10-year follow-up. Depression was measured using the Beck Depression Inventory. The surgical outcome was evaluated using the Oswestry Disability Index, pain evaluation (visual analogue scale), self-reported walking capacity and overall satisfaction with the surgery. Both preoperative life dissatisfaction and the long-term life dissatisfaction burden were associated with poorer 10-year surgical outcomes (i.e. Oswestry Disability Index and visual analogue scale) in logistic regression analyses. Life dissatisfaction was also associated with symptoms of depression. Monitoring subjective well-being, especially life satisfaction and mood, in LSS patients before and after surgery may help in detecting those at risk of a poorer long-term surgical outcome.

Depressive burden is associated with a poorer surgical outcome among lumbar spinal stenosis patients: a 5-year follow-up study.

BACKGROUND CONTEXT: In lumbar spinal stenosis (LSS), conservative treatment is usually the first choice of treatment. If conservative treatment fails, surgery is indicated. Psychological factors such as depression and anxiety are known to affect the outcome of surgery. Previous studies on depression and surgery outcome using long follow-up times are scarce. PURPOSE: The purpose of this study was to investigate the effect of depressive symptoms on the surgical outcome during a 5-year follow-up among patients with LSS. STUDY DESIGN: A prospective observational study. PATIENT SAMPLE: Patient sample included 102 LSS patients who needed surgical treatment. OUTCOME MEASURES: The outcome of surgery was evaluated with the Oswestry Disability Index (ODI), visual analog scale pain assessment, and self-reported walking capacity. METHODS: The patients completed a set of questionnaires preoperatively and 3 and 6 months, as well as 1, 2, and 5 years after the surgery. Depressive symptoms were assessed with the Beck Depression Inventory. The depressive burden was estimated by summing all individual Beck Depression Inventory scores. Statistical analyses included cross-sectional group comparisons and linear regression analyses. No conflicts of interest. RESULTS: On 5-year follow-up, a high depressive burden associated with a poorer outcome of surgery when assessed with the ODI. In linear regression analysis, a high depressive burden associated with higher ODI score. CONCLUSIONS: Even slightly elevated long-term depressive symptoms in LSS patients are associated with an increased risk of a poorer functional ability after decompressive surgery.

Life dissatisfaction burden is associated with a poor surgical outcome among lumbar spinal stenosis patients: a 5-year follow-up study.

Dissatisfaction with life has been found to be associated with somatic health and the short-term surgery outcome in lumbar spinal stenosis (LSS) patients. This study investigated the effects of the long-term life dissatisfaction burden on the surgery outcome in LSS patients with a 5-year follow-up. This was a prospective clinical study. Altogether, 102 patients who underwent decompressive surgery completed a set of questionnaires preoperatively, 3 and 6 months, and 1, 2 and 5 years after the surgery. The final study population at the 5-year follow-up included 67 patients. The mean age of the patients was 67 years and 35% of the patients were men. Life satisfaction was evaluated using a four-item Life Satisfaction Scale. The life dissatisfaction burden was the sum of all six life satisfaction scores recorded during the follow-up. The outcome of surgery was evaluated using the Oswestry Disability Index (ODI), pain evaluation (Visual Analogue Scale; VAS), overall satisfaction with the surgery and self-reported walking capacity. In linear regression, the long-term life dissatisfaction burden was associated with the 5-year ODI, even after adjusting for age, sex, marital status, preoperative ODI and the 5-year VAS. It was not associated with the 5-year VAS score. Monitoring the life satisfaction of surgically treated LSS patients may enable detection of those at risk of a poorer surgery outcome.